Brain pathological changes impair cognition early in disease etiology. There is an urgent need for understanding aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2, also named Fus1, is a mitochondrial-resident protein regulating Ca2+ fluxes to and from mitochondria impacting overall health. We reported that Tusc2-/- female mice develop chronic inflammation and age prematurely, causing age- and gender-dependent spatial memory deficits at 5 m.o. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2-/- female mice demonstrated proinflammatory increase in astrocytes, IFN-γ expression in CD4+T cells and Granzyme-B in CD8+T cells. We also found fewer FOXP3+ T-regulatory cells and Ly49G+ NK and Ly49G+ NKT cells in female Tusc2-/- brain, suggesting a weakened anti-inflammatory response. Moreover, Tusc2-/- hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2+ dynamics. Overall, data suggest that dysregulation of Ca2+-dependent processes and proinflammatory brain microenvironment heighten in Tusc2-/- mice could underlie cognitive impairment. Thus, strategies to modulate the brain’s Tusc2-, Ca2+, and mitochondria-dependent pathways should be explored to improve cognitive health.

In the early decades of the 19th century, the deaf population in the eastern US and Canada was distributed across a vast area. After the 1817 founding of the American School for the Deaf (ASD) in Hartford, CT and the subsequent establishment of schools for the deaf in New York City (NYSD), Philadelphia, and many other US states, hundreds of deaf students called these schools home for several years. After leaving school, the early American Deaf community faced a challenge: How would the community maintain its social and linguistic ties across a vast geographical area once community members had dispersed to their hometowns? In this paper we analyze the attendance registries of two large gatherings of deaf individuals in Hartford in the years 1850 and 1854. These were among the largest and earliest known gatherings of deaf adults. The demographic data included in these registries open a window onto the evolving American Deaf community of the mid-19th century. Our analyses of the attendees’ school affiliations, ages, and marital status show that the signing community that had taken root among students at schools in Hartford and New York persisted among the adult graduates of those schools in towns across the northeastern US. We compare the places of residence of ASD and NYSD alumni in 1850 and 1854 to their hometowns when they first enrolled at school. Our comparisons suggest the mid-19th-century signing community had become more urban; it was centered to a greater extent in populous cities such as New York, Boston, and Hartford than had been true when the attendees had enrolled in school. We consider how the geography of deafness in the 19th century might inform our understanding of the sources of regional variation in ASL. We also consider how early cross-regional interactions may have inhibited such regional variation.

How many different writers authored the huge number of texts attributed to Galen of Pergamum (129~216 AD), medical doctor and philosopher, a giant in the history of medicine? To find out which texts were his and which ones were written by others is known as the “Galenic Question”. We propose a “solution” to it through a multidisciplinary approach based: (a) on historical research and (b) on a mathematical analysis of the Greek texts. The historical approach has considered historical independent sources and anachronisms. The mathematical approach has been based on a mathematical theory concerning deep–language variables, rarely consciously controlled by any author, therefore capable of giving indications on similarity of texts, with little or no bias. The multidisciplinary approach has convinced us that at least three authors wrote the texts attributed to Galen. The first two very likely were real historical persons: (a) a certain Galen living between the end of the I century BC and the second half of the I century AD; (b) the historical Galen of Pergamum (II–III centuries AD) and (c) several unknown authors hiding under the name Galen, but surely living after Galen of Pergamum’s death.

RNA virus polymerases carry out multiple functions necessary for successful genome replication and transcription. A key tool for molecular studies of viral RNA-dependent RNA polymerases (RdRps) is a ‘minigenome’ or ‘minireplicon’ assay, in which viral RdRps are reconstituted in cells in the absence of full virus infection. Typically, plasmids expressing the viral polymerase protein(s) and other co-factors are co-transfected along with a plasmid expressing an RNA encoding a fluorescent or luminescent reporter gene flanked by viral untranslated regions containing cis-acting elements required for viral RdRp recognition. This reconstitutes the viral transcription/replication machinery and allows viral RdRp activity to be measured as a correlate of reporter protein signal. Here we report the first development of a plasmid-based minigenome assay for species A rotavirus, using a firefly luciferase reporter gene.

Nonlocal theories are gaining prominence because they can solve problems which lead to unphysical conclusions in standard models. This study presents a novel fractional boundary element method (BEM) solution for nonlinear nonlocal thermoelastic problems of anisotropic fibrous polymer nanomaterials. This broad BEM solution combines two solutions: anisotropic fibrous polymer nanomaterials problem solution and nonlinear nonlocal thermoelasticity problem solution. The nonlinear nonlocal thermoelasticity problem solution divides the displacement field into complementary component and particular component. The overall displacement is generated using the boundary element technique, which is the solution to a Navier type problem, while the particular displacement is derived using local radial point. The New Modified Shift-Splitting (NMSS) approach, which reduces memory and processing time requirements, was used to solve linear systems created by BEM. Figures demonstrate the numerical findings, which show the effects of fractional and graded parameters on the thermal stresses of nonlinear nonlocal thermoelastic problems of anisotropic fibrous polymer nanomaterials. The numerical results indicate the consistency and efficiency of the proposed methodology.

In order to tackle the issue of severe rocking phenomenon under seismic conditions in structures equipped with steel spring isolation bearings, this paper investigates a novel type of anti-rocking bearing. Firstly, the structural configuration and working principle of the novel anti-rocking bearing are introduced, and a design method for bearing parameters is proposed. Secondly, a finite element analysis model is established using SAP2000 software to conduct nonlinear dynamic time history analysis under seismic loading. The analysis results show that the structural arrangement of the novel anti-rocking bearing reduces both the vertical displacement difference and the rocking angle of the isolation layer. The bearing exhibits a certain level of anti-rocking effect, but it may cause significant tensile forces in some bearings, necessitating the installation of anti-tensile reinforcement. The effectiveness of the anti-rocking effect improves as the stiffness of the steel tension rod in the bearing increases; however, it also leads to higher maximum tension in individual bearings as well as the total tension in all bearings. For structures equipped with the novel anti-rocking bearing, the acceleration amplifies under most cases, with amplification coefficients ranging from 0.82 to 1.55. The performance of the novel anti-rocking bearing varies significantly for different seismic waves. The stiffness of the steel tension rod should be determined considering the reference pressure of the bearing and the maximum designed tension of the bearing. Through the finite element simulation of the bearing, the mechanical properties of the bearing are basically the same as the theoretical analysis results. For the cylinder and the joint bearing, certain structural measures need to be taken to ensure its strength and stiffness.

The classification of kidney tumors has undergone a remarkable evolution since the early 19th century, reflecting advances in medical science and technology. This historical overview traces the development of renal tumor classification, beginning with early clinical observations and macroscopic descriptions to the integration of molecular diagnostics in contemporary classifications. The establishment of international organizations like the World Health Organization (WHO) facilitated collaboration and standardization in tumor classification, leading to refined classifications and standardized nomenclature. Advancements in histological and molecular studies, particularly genetic analyses, revolutionized the understanding of renal cell carcinomas, enabling precise categorization based on molecular characteristics. The journey from rudimentary classifications to sophisticated systems based on detailed histological, immunohistochemical, and molecular criteria underscores the continuous evolution of kidney tumor classification. This article provides a comprehensive overview of this evolution, highlighting the contributions of scholars and the impact of technological advancements on our understanding and management of kidney tumors.

1) Background: Capturing patients’ medical histories significantly influences clinical decisions. Errors in this process lead to clinical errors, increase costs and dissatisfaction among physicians and patients. Physicians in developing countries are overloaded with patients and cannot always follow the proper history-taking procedure. The challenges are acknowledged; however, a comprehensive understanding of the status and the remedies remained unexplored. 2) Objective: This paper aims to investigate the workload, history-taking challenges, and the willingness of the physicians to accept digital solutions. 3) Methods: A cross-sectional online survey was conducted on 104 physicians across Bangladesh, featuring 22 questions regarding their professional environment, workload, digitization status of health records, challenges in history-taking, and attitudes toward adopting digital solutions for managing patient histories; 4) Results: 92.67% of the physicians face workloads, 88.46% struggle in medical history-taking, and only 4.81% use digital medical records. About 70% struggle to complete the necessary history-taking steps, emphasizing the urgent need for solutions. An AI-based Smart Health Gantt Chart (SHGC) system has been introduced for their instant feedback. 93.27% of physicians expressed their willingness to use such a system. 5) Conclusions: The proposed SHGC has the potential to enhance healthcare efficiency in developing nations, benefit physicians, and improve patient-centered care.

Digital machine intelligence has evolved from its inception in the form of computation of numbers to AI, which is centered around performing cognitive tasks that humans can perform, such as predictive reasoning or complex calculations. The state of the art includes tasks that are easily described by a list of formal, mathematical rules or a sequence of event-driven actions such as modeling, simulation, business workflows, interaction with devices, etc., and also tasks that are easy to do “intuitively”, but are hard to describe formally or as a sequence of event-driven actions such as recognizing spoken words or faces. While these tasks are impressive, they fall short in applying common sense reasoning to new situations, filling in information gaps, or understanding and applying unspoken rules or norms. Human intelligence uses both associative memory and event-driven transaction history to make sense of what they are observing fast enough to do something about it while they are still observing it. In addition to this cognitive ability, all bio-logical systems exhibit autopoiesis and self-regulation. In this paper, we demonstrate how machine intelligence can be enhanced to include both associative memory and event-driven transaction history to create a new class of knowledge-based assistants to augment human intelligence. The digital assistants use global knowledge derived from the Large Language Models to bridge the knowledge gap between various participants interacting with each other. We use the general theory of information and schema-based knowledge representation to create the memory and history of various transactions involved in the interactions.

For the first time, an attempt has been made to present in a systematized form chronologically the development of ornithological studies at the National Museum of Natural History in Sofia (Bulgaria) from its foundation in the last decades of the 19th century to the present day. This 135-year period (1889-2024) includes the work of 12 curators of the ornithological collections. Their major contributions and most-significant ornithological publications are also presented.

In this essay, I revisit Neural Networks (NNs) through the lens of evolutionary dynamics. From the two most important features of NNs, I recover the two most general equations of evolutionary dynamics. These two equations may thus serve as a connection between NNs and a body of knowledge that has been built over multiple centuries and has found application across a vast range of disciplines. This connection may therefore also help explain why NNs with the two features in question are applicable across a much broader range of domains than initially envisioned.

Opportunistic networks, an evolution of mobile Ad Hoc networks (MANETs), offer decentralized communication without relying on preinstalled infrastructure, enabling nodes to route packets through different mobile nodes dynamically. However, due to the absence of complete paths and rapidly changing connectivity, routing in opportunistic networks presents unique challenges. This paper proposes a novel probabilistic routing model for opportunistic networks, leveraging nodes' meeting probabilities to route packets towards their destinations. The model dynamically builds routes based on the likelihood of encountering the destination node, considering factors such as last meeting time and acknowledgment tables to manage network overload. Additionally, an efficient message detection scheme is introduced to alleviate high overhead by selectively deleting messages from buffers during congestion. Furthermore, the proposed model incorporates cross-layer optimization techniques, integrating optimization strategies across multiple protocol layers to maximize energy efficiency, adaptability, and message delivery reliability. Through extensive simulations, the effectiveness of the proposed model is demonstrated, showing improved message delivery probability while maintaining reasonable overhead and latency. This research contributes to the advancement of opportunistic networks, particularly in enhancing connectivity and efficiency for Internet of Things (IoT) applications deployed in challenging environments.

A difficult open problem that has never been fully resolved in the literature to date is the behaviour of the (TDCDP) third approximation. As a giant step towards modern control theory, this cutting-edge paper will advance control theory and other relevant inter-disciplinary subjects. Because control theory is important in industry and engineering, this study will be especially beneficial to anyone working in these disciplines who wish to understand more about recent advances in control theory settings. In contrast, the wealth of applications of Fokker Planck Kolmogorov (FPK) equations numerous disciplines As a result, the study instantly gains more taste and credibility. At the end of the paper, there are several challenging open problems, some concluding remarks, and recommendations for further investigation.

Dynamic time history analysis is a powerful and effective method to study the seismic response of tunnels, the dynamic time history to analyze the seismic response of the tunnel in the typical subway in this paper. The analysis results show that the overall levelling of the tunnel will not affect the tunnel too much, and the seismic response of the tunnel is mainly related to the relative displacement of the ground around the tunnel. The analysis results show that the internal force of the tunnel and the tunnel inclination have a good linear relationship, and the tunnel inclination can be used to measure the magnitude of the seismic response of the tunnel.

This article develops a multi-perspective view on motivations and methods for tobamovirus purification through the ages, and presents a novel efficient, easy-to-use approach that can be well-adapted to different species of native and functionalized virions. We survey the various driving forces prompting researchers to enrich tobamoviruses: from the search for the causative agents of mosaic diseases in plants to their increasing recognition as versatile nanocarriers in biomedical and engineering applications. Best practice and also rarely applied options for the serial processing steps required for successful isolation of tobamoviruses are then reviewed. Adaptations for distinct particle species, pitfalls and 'forgotten' or underrepresented technologies are considered as well. The article is topped off with our own development of a method for virion preparation, rooted in historical protocols. It combines selective re-solubilization of polyethylene glycol (PEG) virion raw precipitates with density step gradient centrifugation in biocompatible iodixanol formulations, yielding ready-to-use particle suspensions. This newly established protocol and some considerations for perhaps worthwile further developments could serve as putative stepping stones towards preparation procedures appropriate for routine practical uses of the multivalent soft-matter nanorods.

The vast majority of antibodies generated against a virus will be non-neutralising1. However, this does not denote an absence of protective capacity. Yet, within the field there is typically a large focus on antibodies capable of directly blocking infection (neutralising antibodies, nAbs) of either specific viral strains or multiple viral strains (broadly-neutralising antibodies, bnAbs). More recently, a focus on non-neutralising antibodies (nnAbs), or neutralisation-independent effects of nAbs, has emerged. These can have additive effects on protection or in some cases, be a major correlate of protection. As their name suggests, nnAbs do not directly neutralise infection but instead, through their Fc domains, may mediate interaction with other immune effectors to induce clearance of viral particles or virally infected cells. nnAbs may also interrupt viral replication within infected cells. Developing technologies of antibody modification and functionalisation may lead to innovative biologics that harness the activities of nnAbs for antiviral prophylaxis and therapeutics. In this review, we discuss specific examples of nnAb actions in viral infections where they have known importance. We also discuss the potential detrimental effects of such responses. Finally, we explore new technologies for nnAb functionalisation to increase efficacy or introduce favourable characteristics for their therapeutic applications.

Duct-dependent lesions are classically divided into duct dependent pulmonary circulation which involves severe right sided obstructive lesions such as pulmonary atresia or critical stenosis, and duct dependent systemic circulation which is characterized by malformation of the left side of the heart, and whose severest spectrum is hypoplastic left heart syndrome. Dextro-transposition of the great arteries remains in gray zone between being included in some old classifications as a duct dependent pulmonary circulation lesion or a new category of duct-dependent or independent mixing lesion. We hypothesize that re-classifying duct dependent congenital defects into duct dependent perfusion and oxygenation offers a model to fit D-TGA into the same category of right sided obstructive lesions and reflects the clinical spectrum in a more comprehensive way.

Ionic channels are present in eucaryotic plasmatic and intracellular membranes. They coordinate and control several functions. One of the most diverse ionic channels family are the potassium (K) channels. Within this family are the ATP-dependent potassium channels (KATP), which belong to the potassium rectifier channel family. These channels were initially described in heart muscle, yet they are also present in different types of tissues such as pancreatic, skeletal muscle, brain, and vascular and non-vascular smooth muscle. In ß-pancreatic cells, KATP are primarily responsible for maintaining membrane potential and for the depolarization mediated insulin release. KATP density/activity seems to be determinant in physiological the outcome, in pancreatic cells decrease of this density/activity may be related to Insulin resistance (IR). In extra pancreatic tissues KATP relation with IR is beginning to be explored. It is possible that in skeletal muscle, the KATP are involved in insulin dependent glucose recapture and that KATP activation leads to IR. In adipose tissue, KATP containing Kir6.2, could be related to increase in free fatty acids and insulin resistance, therefore, pathological processes leading to a prolonged adipocyte KATP inhibition might promote obesity related to insulin resistance. In central nervous system KATP activation can regulate peripheric glycemia and lead to brain IR which could be a much earlier manifestation of peripheral alterations that lead to the development of pathologies such as obesity and type 2 diabetes mellitus. In this review we aim to discuss the KATP channel characteristics, its relationship to known clinical disorders and the mechanisms and potential relations with peripheral and central insulin resistance.

LuBO3 crystallizes in the calcite type (CaCO3) structure and is a widely applied inorganic host for luminescent materials and scintillators. Even though many scientific works have been published concerning the optical properties of rare earth doped LuBO3, so far, no study of the emission spectra as function of the excitation energy of such orthoborates has been conducted. Therefore, this work deals with the photoluminescence of RE doped LuBO3 with RE = Ce3+, Eu3+, Gd3+, or Tb3+, while an emphasize is laid on the energy dependence of these four luminescent compounds.

This article describes the history of research and development of surface-penetrating radar, starting from the 60s in the USSR, and ending today in Russia and neighboring states formed after the collapse of the USSR. The outstanding role played in the initial period of this technology development by Prof. M.I. Finkelstein and his colleagues is highlighted. Their research had a significant impact on subsequent developments in modern Russia and the neighboring countries.

Neuronal timing is critical for many brain functions such as perception and learning. At the level of the chemical synapse, the synaptic delay is determined by the presynaptic release probability (Pr) and the waveform of the presynaptic action potential (AP). Depolarization-induced analogue-digital facilitation (d-ADF) is a form of context-dependent synaptic facilitation that is induced by constant depolarization of the presynaptic neuron and is mediated by voltage inactivation of presynaptic Kv1 channels. Whether synaptic delay is modulated during d-ADF remains unclear. We show here that despite Pr is elevated during d-ADF at L5-L5 synapses, the synaptic delay is surprisingly unchanged, suggesting that both Pr- and AP-dependent changes in synaptic delay compensate for each other. We conclude that in contrast with other short- or long-term modulation of presynaptic release, timing is not affected during d-ADF because of the opposite interaction of Pr- and AP-dependent modulations of synaptic delay.

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs repurposed for treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule binding to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and other Arbidol derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest quality SPR binding data to S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results from molecular docking and modeling the structure-activity-relationship (SAR) of a newly reported series of Clofazimine derivatives supports the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure-sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronavirus such as (SARS-CoV, MERS, hCoV-229E, hCoV-OC43).

Since the beginning of the COVID-19 pandemic, extensive drug repurposing efforts sought to identify small molecule antivirals with various mechanisms of action. Here we aim to review research progress on small molecule viral entry and fusion inhibitors that directly bind to the SARS CoV-2 Spike protein. Early in the pandemic, numerous small molecules were identified in drug repurposing screens and reported to be effective in vitro SARS CoV-2 viral entry or fusion inhibitors. However, given minimal experimental information regarding the exact location of small molecule binding sites on Spike, it was unclear what the specific mechanism of action was, or where the exact binding sites were on Spike for some inhibitor candidates. The work of countless researchers has yielded great progress, with the identification of many viral entry inhibitors that target elements on the S1 receptor binding domain (RBD) or N-terminal domain (NTD) and disrupt S1 receptor binding function. In this review, we will also focus on highlighting fusion inhibitors that target inhibition of the S2 fusion function, either by disrupting the formation of the postfusion S2 conformation or alternatively by stabilizing structural elements of the prefusion S2 conformation to prevent conformational changes associated with S2 function. We highlight experimentally validated binding sites on the S1/S2 interface and on the S2 subunit. While most mutations to the Spike protein to date in variants of concern (VOCs) have been localized to the S1 subunit, the S2 subunit sequence is more conserved with only a few observed mutations in proximity to S2 binding sites. Several recent small molecules targeting S2 have been shown to have robust activity over numerous recent VOC mutant strains and/or greater broad spectrum antiviral activity for other more distantly related coronaviruses.

A burgeoning body of scholarship identifies and discusses botanic gardens as increasingly important centres of biodiversity conservation and sustainability. Notwithstanding the high quality and richness of this literature, it encompasses relatively autonomous fields of expertise that are neither designed nor expected to promote cross-disciplinary, integrative, accounts of botanic gardens as institutions of conservation and sustainability. Bridging key aspects of the botanic garden literature, this article brings into conversation historical accounts with contemporary scholarship on the matter. In so doing, it unveils dilemmas and challenges faced by botanic gardens as they grapple with their historic legacies, but also renew their relevance in nurturing sustainable socio-environmental futures. The article proceeds by covering three focal points. First, it summarizes the scholarly literature on the history of botanic gardens. Second, it presents accounts of current scientific and biodiversity conservation endeavours as reflexive engagements with their historical legacies. Third, it addresses the recent emergence of socio-cultural missions at botanic gardens as a significant step beyond their historical focus on plants and plant ecosystems.

This paper revisits the analytical theory of fractional vibrations with the highlights in five aspects. First, we address the cases of structures with frequency dependent mass or damping or stiffness in Sections 2-4. Second, we introduce the theory based on the general second-order vibration motion equation with frequency dependent elements (mass, damping, stiffness) in Sections 5-7. Third, we present the analytical theory of seven specific classes of second-order vibration systems with frequency dependent mass or damping or stiffness in Sections 8 and 9. Fourth, we bring forward the analytical theory of seven classes of fractional vibration systems in Sections 10-12. Finally, as an application, we give the closed form expression of the forced response to multi-fractional Euler-Bernoulli beam in Section 13. The explanation of the nonlinearity of fractional vibrations is given in Section 14.

Epithelial–mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been extensively investigated in developmental biology and pathology. More than a half-century of EMT study has made it a large research field and a mainstream concept. However, discrepancies and disputes over EMT and EMT research have also grown over time. Particularly, neither the epithelial and mesenchymal states/properties nor their regulatory networks nor specific markers have been defined, rendering the EMT, MET and EndMT concepts groundless. EMT and MET effects represented by the change in cell shapes or adhesiveness or symbolized by EMT factors are biased interpretation of the overall change in cellular property and regulatory networks during developmental process and cancer progression. The true meaning of EMT effects in some developmental and pathological processes, such as fibrosis, needs re-evaluation. But the core EMT factors are actually a few components of the regulatory networks of neural stemness, which determines tumorigenicity and pluripotency. The EMT effects in cancer progression and neural crest formation are wrong attribution of the role of neural stemness during cancer progression and the cell-intrinsic property of neural crest cells to the unknown mesenchymal state. It is time to reassess the significance of EMT and its related concepts in scientific research.

This paper focuses on the paradigm that explains the link between energy transitions and financial transformations. In particular, it attempts to shed some light on the following question: How did the transition from wood to coal affect financial development in late 18^th and early 19^th century Britain? The results demonstrate that the energy transition in Britain during the 1^st Industrial Revolution constituted an important moment in the country's financial development and can be used as an example of how an energy innovation can foster the financial development of particular countries or regions.

The hard open problem of finding the lower bound for the Fokker Planck Kolmogorov’s time-dependent controller parameter probability density function is addressed for the first time in literature in this work. This revolutionary exposition will put control theory and other related inter-disciplinary fields to a higher level towards contemporary control theory. Notably, based on the influential role of control theory in both engineering and industry, this paper will be of great value to all engineering and industry professionals who seek to know more about advanced trends within control theory settings. On the other remit of the spectrum, Fokker Planck Kolmogorov(FPK) equations are of high importance to physicists as well as mathematicians, based on their multiple applicability to multi-interdisciplinary fields of human knowledge, and beyond. So, this by default adds more taste and credibility to this study. Concluding thoughts are included at the end of the work along with a difficult outstanding problem and the direction of future work.

This work is the first in literature to tackle the difficult open problem of determining the upper bound and threshold theorem for the TDCDP (time-dependent controller parameter) of the (Fokker Planck Kolmogorov) probability density function. This revolutionary exposition will put control theory and other related inter-disciplinary fields to a higher level towards contemporary control theory. Notably, based on the influential role of control theory in both engineering and industry, this paper will be of great value to all engineering and industry professionals who seek to know more about advanced trends within control theory settings. On the other remit of the spectrum, Fokker Planck Kolmogorov(FPK) equations are of high importance to physicists as well as mathematicians, based on their multiple applicability to information theory, graph theory, data science, finance, economics, and beyond. So, this by default adds more taste and credibility to this study. This leads by nature to introducing a different flavor to this ground-breaking research by highlighting the impact of Fokker Planck Kolmogorov(FPK) to revolutionize crypocurrency,which have received its name because it uses encryption to verify transactions, a new debatable digital payment system that doesn't rely on banks to verify transactions. It’s a peer-to-peer system that can enable anyone anywhere to send and receive payments. The paper ends with closing remarks combined with some challenging open problems and the next phase of research.

The significance of Kashmir conflict as one of the world’s longest running conflicts has frequently drawn the attention of both communication and international relations’ scholars which makes it an important issue from the perspective of interdisciplinary approach. The researchers have attempted to assemble a brief history of the Indian held Jammu and Kashmir Conflict from the time of partition in 1947 to the developments which took place till 2019 in the light of the available literature. The paper provides substantial historical context of the important events like instrument of accession, UN resolutions on Kashmir conflict, Simla Accord, Gawkadal Massacre , Lahore Declaration, Kargil War, killing of Burhan Wani, Uri attack and Article 370’s abrogation .

To resolve problems in the dietary life of university athletes, education is essential for enabling athletes to change their own dietary behavior. The purpose of this research, it was decided to verify the effectiveness of sports nutrition education based on self-determination theory (SDT). Methods, the subjects were thirty-six male university rowers. A stratified randomized comparison test was conducted by student year (SDT group and control group). Sports nutrition education was held three times, via an Internet conferencing system. Furthermore, group work over social media was used for the SDT group. Four evaluations were carried out based on anthropometric measurements, brief-type self-administered diet history questionnaire (BDHQ),sports nutrition knowledge (SNK), and treatment self-regulation questionnaire (TSRQ). Results, for the intra-group factor "Protein," a significant difference was evident in the self-determination theory group (50.0±28.5, 78.6±28.1, 81.0±21.5, p<0.000, units: %), and there were significant differences between after and before, and between three months after and before (p=0.002, p=0.002). For BDHQ, significant differences were evident for green/yellow vegetables, fruits, and dairy between after and before for the self-determination theory group (159.1±74.2-126.7±70.6, p=0.009, 306.0±196.2-195.2±146.1, p=0.020, 257.0±147.0-183.3±167.9, p=0.040, units: g). In conclusion, sports nutrition education based on SDT improved dietary knowledge and increased dietary intake.

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently SARS-CoV-2, al-ready four other coronaviruses have been circulating in the human population. The alpha coronaviruses NL63 and 229E and the beta coronaviruses OC34 and HKU1. These circulating coronaviruses all cause mild respiratory illness during the winter seasons and most people are already infected in early life. Could antibodies and/or T cells, es-pecially against the beta coronaviruses have offered some form of protection against SARS-CoV-2? Related is the question whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory, generated during the SARS-CoV-2 pandemic, ei-ther by infection or vaccination offer protection against future coronaviruses? Or rather than protection, could antibody dependent enhancement have taken place, a mecha-nism by which circulating corona antibodies enhance the severity of COVID-19? An-other related phenomenon, the original antigen sin, would also predict that the effec-tivity of the immune response to future coronaviruses would be impaired because of reactivation of memory against irrelevant epitopes. Current available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses.

The reliability of concrete cable-stayed bridge structure is time variant. This is due to strength deterioration and time-variant mechanical and environmental loadings. Demands for keeping concrete cable-stayed bridge structure in functional and reliable states require maintenance interventions. Limited financial resources require optimal maintenance strategies. These strategies have to consider the effects of uncertainties not only on the structural reliability deterioration but also on the maintenance interventions. By analyzing variation of concrete cable-stayed concrete cable-stayed bridge liabilities and benefit expectation through different maintenance programs, on the condition of satisfying the concrete cable-stayed bridge performance, with the maximum expected benefit as the target to discuss repair and reinforcement strategies for the concrete cable-stayed bridges in service. The method takes into account the present performance and future expected benefit, optimizing the performance of the concrete cable-stayed bridge and the expected benefit through determination policies of concrete cable-stayed concrete cable-stayed bridge maintenance program. The proposed method also includes an advanced cost model which takes into account the interaction between costs of maintenance interventions and their effect on reliability. Examples are presented demonstrating the application of the proposed method to a stock of existing deteriorating concrete cable-stayed bridges under various maintenance scenarios.

There is a rich history of cancer treatments which provides a number of important lessons for present and future cancer therapies. We outline this history by looking in the past, reviewing the current landscape of cancer treatments, and by glancing at the potential future cancer therapies.

Viruses continue to provide vital insights into the field of control of gene expression. Viral transactivators, in concert with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to trans-acting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the Replication-Transcription complex might, therefore, transactivate viral and cellular RNAs in transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution, constituting a potential pan-coronaviral therapeutic target. Here, we show by using primary and secondary structural comparisons that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3, the coronaviral nucleocapsid C-terminal domains (N-CTDs) harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and the coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain similar to that in lentiviral Tat proteins.

An exposition is undertaken to reveal the significant impact of the time-dependent root parameter, on the stability of Pointwise Stationary Fluid Flow Approximation (PSFFA) model of the non-stationary queueing system. This opens new grounds to stability analysis of non-stationary queueing systems. Potential PSFFA applications of IoT are highlighted.

Architectural Education (AE), as a multidisciplinary field of knowledge, has been through various learning forms, and several learning theories have been adapted to respond to progressive change in the learning environment context and increasing demand for a sustainable built environment. However, it is noticeable that there needs to be more research collaboration efforts among architecture schools and more focus on practice sessions in AE. Therefore, this systematic literature review intends to synthesize the most dominant challenges and examine trends in AE during the early decades of the twenty-first century. This study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as the review protocol. The keywords have been identified and searched in Scopus and Web of Science (WoS) databases. The authors analyzed ninety-six articles between 2000 and 2023 based on the inclusion and exclusion criteria. The analysis of the relevant articles provided valuable insights into research intention. The review reveals the four main themes in AE, namely (1) learning approaches, (2)technology innovation, (3) sustainability, and (4) history. Furthermore, the researchers discuss experiential learning, blended learning, e-learning, and online learning as the most used learning methods in architecture schools. More research on art, social context, and the physical built environment seems crucial for enhancing AE. This study comprehensively reviews the state of the art on AE by interpreting the most dominant architectural issues and learning challenges. The outcome is valuable for improving the learning environment in architecture schools.

Introduction: The first velvet worm (phylum Onychophora) was described nearly two centuries ago, by a British priest, in the tiny Caribbean island of Saint Vincent. He thought it was a new type of mollusk, a slug with tiny feet. Objective: Here I present a brief biographical account of the field of onychophorology, marking nearly two hundred years since the first scientific description of velvet worms. Method: I synthetize historical records, publications, personal experience and biographical sketches to construct an encompassing narrative of the field's development through the lives of researchers who have shaped it. Results: The narrative begins with Lansdown Guilding's initial discovery and extends to include pivotal figures like Jean Victor Audouin, Charles Émile Blanchard, Adolph Eduard Grube, Lorenzo Camerano, Eugène Louis Bouvier, Sidnie Milana Manton, Sylvia S. Campiglia, Roger Lavallard, Hilke Ruhberg, and Bernal Morera-Brenes. Contributions from Noel Tait, Robert Mesibov, Georg Mayer, Cristiano Sampaio, Ivo de Sena Oliveira, and José Pablo Barquero-González are also acknowledged. The article highlights their individual contributions to onychophorology, considering their scientific achievements and personal journeys, and presents portraits of nearly all of them. Conclusion: Our current knowledge of onychophorans is the results of hundreds of contributions from a large number of people who have lived varied, sometimes fascinating lives, but all united in their interest in velvet worms.

Animal trypanosomiasis (AT) is a complex of veterinary diseases known under various names such as nagana, surra, dourine and mal de caderas, depending on the country, the infecting trypanosome species and the host. AT is caused by parasites of the genus Trypanosoma, and the main species infecting domesticated animals are T. brucei brucei, T. b. rhodesiense, T. congolense, T. vivax, T. evansi and T. equiperdum. AT transmission, again depending on species, is through tsetse flies or common Stomoxys and tabanid flies or through copulation. Therefore, the geographical spread of all forms of AT together is not restricted to the habitat of a single vector like the tsetse fly and currently includes almost all of Africa, and most of South America and Asia. The disease is a threat to millions of companion and farm animals in these regions, creating a financial burden in the billions of dollars to developing economies as well as serious impacts on livestock rearing and food production. Despite the scale of these impacts, control of AT is neglected and under-resourced, with diagnosis and treatments being woefully inadequate and not improving for decades. As a result, neither the incidence of the disease, nor the effectiveness of treatment is documented in most endemic countries, although it is clear that there are serious issues of resistance to the few old drugs that are available. In this review we particularly look at the drugs, their application to the various forms of AT, and their mechanisms of action and resistance. We also discuss the spread of veterinary trypanocide resistance and its drivers, and highlight current and future strategies to combat it.

Cultures in Mediterranean climate zones (MCZs) around the world have long been reliant on groundwater and springs as freshwater sources. While their ecology and cultural sustainability are recognized as critically important, inter-relationships between springs and culture in MCZs has received little attention. Here we augmented a global literature review with case studies in MCZ cultural landscapes to examine the intensity of cultural and socio-economic impacts on springs ecohydrogeology. MCZs are often oriented on the west and southern coasts in tectonically active landscapes, which control aquifer structure, the prevalence of westerly winds, and aridity, and generally expose associated habitats to harsh, afternoon sunlight. Cultural appreciation and appropriation of springs ranges widely, from their use as subsitence supplies to profound traditions, such as Greco-Roman nymphs, and Asian and Abrahamic spiritual cleansing and baptism. Commoditization of water resources for agriculture, industry (e.g., mining, water bottling, geothermal resorts), and urban needs is placing ever-increasing, non-sustainable demands on aquifers and springs. When economic values approach or exceed cultural values, these irreplaceable aquatic resources are degraded and lost. Sustainable stewardship of springs and the aquifers that support them are a little-recognized, but central conservation challenge for modern society facing global climate changes.

Abstract: Earth’s Phanerozoic history is marked by about 100 major events (“golden spikes”) indicating the beginnings of new stages in the Geologic Time Scale (GTS). Stage boundaries signify major deterministic events that are relatively well-known and can be correlated worldwide, mostly on the basis of appearances or disappearances of fossil species. The latest stage (Anthropocene) is human-made and currently involves rapid (approximately linear) increase in average atmospheric temperature. The main cause of Earth’s past and current temperature increases is addition of CO2 to the atmosphere. There is continuous exchange of greenhouse gases between atmosphere and oceans, which (per unit of volume) contain 50 to 60 times as much CO2 as the atmosphere. Abundance of new very precise worldwide observations is allowing multifractal modeling of weather and climate during the latest Quaternary stages during which some variables like temperature of the atmosphere and frequency of forest fires can be described by using the Pareto-lognormal frequency distribution model with parameters that are subject to continuous (deterministic) changes, similar to those in the earlier Phanerozoic.

This paper maps the causes of the demographic, economic and social decline of a selected border micro-region during the last century. The decline occurred due to the location being remote, lacking natural resources and having an unsuitable industrial structure. Historical events associated with the post-war deportation of the German population and efforts to create a classless society also played a role in the decline. The results are an 87% population decrease, the demise of most companies, a very low level of human capital and unemployment reaching up to 5%. In order to comprehend the current state of the border micro-region and predict future development, it is necessary to understand the development that has occurred since approximately the middle of the nineteenth century. The European countryside is certainly not homogeneous, and different regions have shown unique mixes of positional, natural, economic and political factors. Some hope has been raised in relation to the transition to a post-productive economy, a transition that turns the remoteness of the region into an advantage. This is confirmed by the positive migration balances of the smallest municipalities in the last decade.

a Special Issue of Microorganisms devoted to ‘Microbial Biocatalysis and Biodegradation’ would be incomplete without some form of acknowledgement of the many important roles that dioxygen-dependent enzymes (principally mono- and dioxygenases) play in relevant aspects of biooxygenation. This is reflected by the multiple strategic roles that dioxygen -dependent microbial enzymes play both in generating valuable synthons for chemoenzymatic synthesis, and in facilitating key reactions that drive the global geochemical Carbon Cycle. A useful insight into this relationship can be gained by reviewing the evolution of the current status of 2,5-diketocamphane 1,2-monooxygenase (EC 1.14.14.108) from camphor-grown Pseudomonas putida ATCC 17453. Over the last sixty years, the perceived nature of this monooxygenase has transmogrified significantly. Commencing in the 1960s, extensive initial studies consistently reported that the enzyme was a monomeric true flavoprotein dependent on both FMNH₂ and nonheme iron as bound cofactors. However, over the last decade all those criteria have changed absolutely, and the enzyme is currently acknowledged to be a metal ion-independent homodimeric flavin-dependent two-component monooxygenase deploying FMNH₂ as a cosubstrate. That transition is a paradigm of the ever evolving nature of scientific knowledge.

The article suggests that the the Gregorian calendar is unscientific and ivestiagtes why the Vaidika Pañcāṅga is mathematically accurate. It is a qualitative study and the library method of research has been carried out to support the claims. For Indic words, the International Alphabet for Sanskrit Transliteration (IAST) method is used.

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and as such provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may results in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn2+. Members of this HDAC group are involved in the epigenetic regulation primarily via modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extra nuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases and we will discuss the potential of their inhibitors for lung injury prevention.

Oxygen extraction fraction (OEF), the fraction of oxygen that tissue extracts from blood, is an es-sential biomarker for directly assessing tissue viability and function in neurologic disorders. For quantitative mapping of OEF, an integrative model of quantitative susceptibility mapping and quantitative blood oxygen level-dependent magnitude (QSM+qBOLD or QQ) was recently pro-posed. However, QQ assumes Gaussian noise in both susceptibility and multi-echo gradient echo (mGRE) magnitude signals for OEF estimation. This assumption is unreliable in low sig-nal-to-noise ratio (SNR) regions like disease-related lesions, risking inaccurate OEF estimation and potentially impacting clinical decisions. Addressing this, our study presents a novel multi-echo complex QQ (mcQQ) that models realistic noise in mGRE complex signals. The proposed mcQQ was implemented using a deep learning framework (mcQQ-NET) and compared with the existing deep learning-based QQ (QQ-NET) in simulations, ischemic stroke patients, and healthy subjects. Both mcQQ-NET and QQ-NET used identical training and testing datasets and schemes for a fair comparison. In simulations, mcQQ-NET provided more accurate OEF than QQ-NET. In the sub-acute stroke patients, mcQQ-NET showed a lower average OEF ratio in lesions relative to unaf-fected contralateral normal tissue than QQ-NET. In the healthy subjects, mcQQ-NET provided uniform OEF maps, similar to QQ-NET, but without unrealistically high OEF outliers in areas of low SNR. Therefore, mcQQ-NET improves OEF accuracy by better reflecting realistic data noise characteristics.

Aims. In a male Italian cohort (initially aged 40-59, n=1712) followed-up during 61 years and reaching practical extinction, the natural history of major CVD mortality categories including coronary heart disease (CHD), stroke and other Heart Diseases of Uncertain Etiology (HDUE, including congestive heart failure) were studied along with their risk factor relationships. Methods and Results. Cox models were run with 12 covariates measured at entry as possible predictors. About 93% of all CVD deaths were covered by the 3 major groups selected here (N=751): 37.4% of them were diagnosed as CHD, 30.6% as stroke and 28.5 % as HDUE. CHD declined in the last 20 years of follow-up, while a sharp increase of HDUE mortality was seen. Baseline mean levels of serum cholesterol were 209.6, 204.2 and 198.0 mg/dl respectively for CHD, stroke and HDUE deaths: the multivariable coefficients of serum cholesterol were positive and significant for CHD (p<0.0001) and stroke (p=0.0203) and not significant for HDUE (p=0.3467). In Fine-Gray models, the algebraic signs of cholesterol coefficients were opposite for CHD versus the other mortality categories (t=3.13). The predictive performances of remaining risk factors were varied whereas that of Cox models was not very good, probably due to the attrition phenomenon and possible competing risks. Conclusion. Large differences in natural history and risk factors were found comparing the 3 CVD conditions, potentially indicating different etiologies and pointing to the need of not mixing them up in a grouped CVD category.

The assessment of Health-Related Quality of Life (HRQoL) in Thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of Transfusion-Dependent Thalassemia (TDT) patients in Greece. This was a multicentre, cross-sectional study conducted in 2017, involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower, compared to the general population in Greece. The mean summary score of TranQol was relatively high (71±14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment in a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups.

The Republic of Venice was one of the longest-lived states in modern history, and its stability and survival has been studied through many different angles, and one of them is to try and find pivotal moments in its history that explain it, or its eventual demise. In this paper, through the rigorous statistical analysis of the dataset of marriages by nobles in the Republic, we will try to define a methodology for the detection of these events through mono and multivariate change point analysis, and validate that methodology through cross-validation of different procedures, as well as matching the results to historical events. Our analysis shows that these change points occur with statistical significance and that they match political and historical events. These results can be built upon for a better understanding of the historical causes of the success and failure of the Republic of Venice and, by extension, other states.

One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ42 containing isomerized Asp7 residue (iso-Aβ42) and Aβ42 containing phosphorylated Ser8 residue crossed the BBB better than unmodified Aβ42, which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ42 an order of magnitude weaker than to Aβ42. Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.

The study’s objective is to analyse the mechanical properties of steel pipe piles as a part of a trestle bridge subjected to five years of natural marine corrosion degradation. Sixteen tensile specimens were extracted from the steel pipe piles in the splash, tidal, and immersion zones. The experimental tensile test results are used to establish regression equations defining elastic modulus, yield strength, strain hardening index, and strength coefficient for the true stress-strain curves of the three regions. A non-linear time-dependent mathematical model is exploited to identify the corrosion degradation using the data from one single corrosion degradation measurement campaign. The analysis indicated that the splash zone experiences the most severe corrosion degradation, and there are progressive losses in the mechanical properties of each zone as the corrosion degradation progresses. The established relationships of the mechanical properties, as a function of the ratio of corroded plate thickness to the as-built one, can be used as a fast-engineering approach to identify the mechanical properties of severely corroded piles. The corrosion degradation allowance is also defined using the First Order Reliability Method, accounting for existing uncertainties covered by the partial safety factors. By examining the impact of marine corrosion on the mechanical properties of marine structures and developing predictive models to assess the corrosion’s effect on material strength and corrosion allowance, the study aims to improve offshore structures’ safety, design, and maintenance.

Spin-orbit coupling and nonparaxiality effects during propagation of vortex vector light beams in a cylindrical graded-index waveguide are investigated by solving the full three-component field Maxwell’s equations. Symmetry breaking effects for left- and right-handed circularly polarized vortex light beams propagating in a rotationally symmetric graded-index optical fiber are considered. The mode-group delay in a graded-index fiber due to spin-orbit interaction is demonstrated. It is shown that the relative delay times between vortex pulses of opposite circular polarizations of the order of 10 ps/km can be observed in graded-index fibers for high-order topological charges.

This article deals with a finite-source stock-dependent stochastic inventory system with heterogeneous servers and retrial facility. The system can store up to S number of items, and the lifetime of each item follows an exponential distribution. The primary customers arrive in a finite waiting hall from a finite source and get service from the multi-channel (c-heterogeneous servers). The customer’s arrival rate depends on the present stock level. Those customers who arrive while the waiting hall is full enter into the finite orbit. Also, customers in the waiting hall can become impatient and enter the orbit. The (s,Q) ordering policy is adopted for the replenishment of stocks. In the steady state, the joint probability distribution of a number of items in the inventory, busy servers, customers in the waiting hall, and orbit is computed. The comparative numerical analysis of heterogeneous and homogeneous servers on the expected total cost, the average number of customers in the waiting hall and orbit, the fraction of successful retrial rate, and the average impatient customer rate are also carried out.

Hepatitis E virus is a major etiological agent of chronic hepatitis in immunosuppressed individuals. Studies on HEV in the context of liver transplantation have produced mixed results, most of the data coming from studies conducted in high-income countries. This was a prospective cohort study of liver transplant recipients in southeastern Brazil. Recipients were systematically followed for one year, with the objective of determining the prevalence, incidence, genotype, and natural history of HEV infection in this population. We included 107 liver transplant recipients and 83 deceased donors. Positivity for anti-HEV IgG was detected in 11 (10.2%) of the recipients and in eight (9.7%) of the donors. None of the patients tested positive for HEV RNA at baseline or during follow-up. There were no episodes of reactivation or seroconversion, even in cases of serological donor-recipient mismatch or in recipients with acute hepatitis. Acute and chronic HEV infections seem to be rare events in the region studied. That could be attributable to social, economic, and environmental factors. Our data indicate that, among liver transplant recipients, hepatitis E should be investigated only when there are elevated levels of transaminases with no defined cause, as part of the differential diagnosis of seronegative hepatitis after transplantation.

Replication stress (RS) is a characteristic state of cancer cells as they tend to exchange precision of replication for fast proliferation and increased genomic instability. To overcome the consequences of improper replication control malignant cells frequently inactivate parts of their DNA damage response (DDR) pathways (the ATM-CHK2-p53 pathway), while relying on other pathways which help to maintain replication fork stability (ATR-CHK1). This creates a dependency on the remaining DDR pathways, vulnerability to further destabilization of replication and synthetic lethality of DDR inhibitors with common oncogenic alterations such as mutations of TP53, RB1, ATM, amplifications of MYC, CCNE1 and others. The response to RS is normally limited by coordination of cell cycle, transcription and replication. Inhibition of WEE1 and PKMYT1 kinases, which prevent unscheduled mitosis entry, leads to fragility of under-replicated sites. Recent evi-dence also shows that inhibition of Cyclin-dependent kinases (CDKs), such as CDK4/6, CDK2, CDK8/19 and CDK12/13 can contribute to RS through disruption of DNA repair and replication control. Here, we review the main causes of RS in cancers as well as main therapeutic targets – ATR, CHK1, PARP and their inhibitors.

Two-dimensional (2D) materials show advantages as surface enhanced Raman scattering (SERS) substrate over traditional noble metals, such as chemically inert flat surface and uniform SERS signals. However, due to the low density of free electrons of 2D materials, the enhancement mechanism is mainly restricted to chemical enhancement instead of electromagnetic enhancement, resulting a relatively low enhancement factor. In this work, we reported a sensitive 2D SERS substrate based on chemical vapor deposited MoN nanosheets with electromagnetic enhanced mechanism. The maximum enhancement factor can be 3×105 with a limit of detected concentration of 4×10-8 M, which is comparable to those noble metal SERS substrates without hot spots. The MoN nanosheets show strong surface plasmon resonance in the visible range as evidenced by the UV-vis absorption spectroscopy and first principle calculation. The MoN nanosheets SERS substrates exhibit excellent Raman signal uniformity within the nanosheets. Meanwhile, Distinct thickness dependent sensitivity was observed in the MoN nanosheets, higher sensitivity can be achieved by decreasing the thickness of the nanosheets. Furthermore, the MoN nanosheets SERS substrate also show high thermal stability, which can be annealed in air for more than 300℃ and maintain its SERS activity. The high stability of MoN nanosheets allows it to be reused for 20 cycles without obvious signal decay. The high sensitivity, stability, reusability and Raman signal uniformity, makes MoN nanosheets an ideal 2D SERS substrate for practical applications.

Esophagogastric cancers are among the most common and deadly cancers worldwide. This review traces their chronology from 3000 BCE to the present. The first several thousand years were devoted to palliation, before advances in operative technique and technology led to the first curative surgery in 1913. Systemic therapies were introduced in 1910, and radiotherapy shortly thereafter. Operative technique improved massively over the 20th century, with operative mortality rates reducing from over 50% in 1933 to less than 5% by 1981. In addition to important roles in palliation, endoscopy became a key non-surgical curative option for patients with limited-stage disease by the 1990s. The first nonrandomized studies on combination therapies (chemotherapy +/- radiation +/- surgery) were reported in the early 1980s, with survival benefit only for subsets of patients. Randomized trials over the next decades had similar overall results, with increasing nuance. Disparate conclusions led to regional variation in global practice. Starting with the first FDA approval in 2017, multiple immunotherapies now encompass more indications and earlier lines of therapy. As standards of care incorporate these effective yet expensive therapies, care must be given to disparities and methods for increasing access.

Flavin-dependent monooxygenases (FMOs) have made substantial influence as catalysts for monooxygenation reactions, impacting diverse field such as drug metabolism, environmental studies, and natural product synthesis. Their application in biocatalysis boasts several advantages over conventional chemical catalysis, such as heightened selectivity, safety, sustainability, and eco-friendliness. In the realm of biomedicine, FMOs are pivotal in antibiotic research, modulating natural products, antimicrobial agents, and pathways involved in drug synthesis. They're also underscored as potential pharmaceutical targets, pivotal in disease progression and viable for therapeutic intervention. Additionally, FMOs play a substantial role in environmental science, especially in pesticide processing and plant vitality. Their involvement in biosynthesizing compounds like polyethers, tropolones, and ω-hydroxy fatty acids, with remarkable regio- and stereoselectivity, renders them indispensable in drug discovery and development. As our comprehension of FMOs' catalytic mechanisms and structures advances, coupled with cutting-edge biotechnologies like computational design and directed evolution, FMOs are poised to occupy an increasingly significant role in both scientific exploration and industrial applications.

The case of naturalization of the zebra mussel, Dreissena polymorpha (Pallas), in coun-tries lying beyond its native Ponto-Caspian range is remarkable as one of the first instances, when the scientific community as early as the mid-19th century was fully aware of the non-indigenous status of a particular species as well as of the need for the study and monitoring of this process. Based on a study of contemporary sources, I reconstruct the early response of the European naturalists (including those that today would be called ‘citizen scientist’) to the invasion of Dreissena and describe their attitudes to the problem, including the divergence of opinion about the origin and the means of dispersal of this bivalve species. An analysis of pa-pers of the English, French, German, and Russian authors published between 1774 and 1920 has shown that the invasion of D. polymorpha was by no means ‘silent’; quite opposite, it provoked an immediate reaction of naturalists, and the scientific agenda for the study of the new invader was proposed in England as early as 1838

We consider a Cauchy problem for differential equations in a Hilbert space $X$. The problem is stated in a time interval $I$, which can be finite or infinite. Weuse a fixed point argument for history-dependent operators to prove the unique solvability of the problem. Then, we state and prove convergence criteria for both a general fixed point problem and thecorresponding Cauchy problem. These criteria provide necessary and sufficient conditions on a sequence $\{u_n\}$ which guarantee its convergence to the solution of the corresponding problem, in the space of both continuous and continuously differentiable functions. We then specify our results in the study of a particular differential equation governed by two nonlinear operators. Finally, we provide an application in viscoelasticity and give a mechanical interpretation of the corresponding convergence result.

The emergence of the semiconductor industry in the early 1960s resulted in a significant stage in the evolution of computing when large computational problems, as typified by the application of the discrete Fourier transform (DFT) to the task of spectrum estimation, could suddenly, with the availability of suitable algorithms, be solved in close to real time fashion. This paper provides a brief and meandering account of the history of the DFT’s various solutions, referred to generically as the fast Fourier transform (FFT), the algorithm being chosen for its mathematical elegance, practical significance and ever‑increasing range of applications. We touch upon a few of the most striking personalities, places and events that were encountered along the way and look, in particular, at the recent British contribution to the journey.

In physics, thought experiments are impressive heuristic tools. They are valuable instruments to help scientists find new results and to teach students the known ones. However, as we shall show, they should always be received with prudence, even when they are a shortcut to 'prove' well-established results. Here, we show that the most widely known thought experiments devised to derive the gravitational frequency shift from energy conservation are, in fact, problematic. When properly set and correctly read, those thought experiments reveal that the existence of the gravitational frequency shift is, in fact, at odds with energy conservation. We also propose two new simple thought experiments, one using the conservation of energy and the other the conservation of linear momentum, that corroborate that conclusion, showing that those conservation principles do not imply the gravitational frequency shift. We think that our results may be of some epistemological interest and could serve as a warning sign on how thought experiments should be received and trusted.

Intracranial compliance (ICC) plays a pivotal role in understanding the underlying mechanisms of various brain disorders and is of great clinical importance. Therefore, addressing the challenges in practical application of ICC is crucial for neurosurgeons. This study explored the significance of ICC assessment considering the time-dependency of specific brain disorders through two distinct approaches: short and large time elapsed (TE) in measuring volume or intracranial pressure (ICP) changes in the ICC equation (∆Volume/∆ICP). Variations in ICC values were observed across various ICC assessment methods and different TE values. Notably, the compensatory response of the brain exhibited non-monotonic and variable changes in a large TE for certain brain disorders, diverging from patterns observed in short TE assessments. Furthermore, the recovery behavior of the brain changed under different brain disorders when exposed to short and long TE conditions. These findings emphasized the dynamic nature of ICC and provided valuable insights into the correct practical assessment of ICC by selecting the appropriate TE, as well as considering the differences in strain rates and loading durations on the brain in different brain disorders. These insights also shed light on the reasons why, despite its clinical significance, ICC monitoring has not yet become a standard component of clinical care, unlike ICP monitoring.

From the first isolation of the cystovirus bacteriophage Φ6 from Pseudomonas syringae 50 years ago, we have progressed to a better understanding of the structure and transformations of the many parts of the virion. The three-layered virion encapsulating the tripartite double stranded RNA (dsRNA) genome, breaches the cell envelope on infection, generates its own transcripts, and coopts the bacterial machinery to produce its proteins. The generation of new virions starts with a procapsid with a contracted shape, followed by packaging single stranded RNA segments with concurrent expansion of the capsid, and finally replication to reconstitute the dsRNA genome. The outer two layers are then added, and the fully formed virions released by cell lysis. Most of the procapsid structure composed of the proteins P1, P2, P4 and P7 is now known, as well as its transformations to the mature, packaged nucleocapsid. The outer two layers are less well studied. One additional study investigated the binding of the host protein YajQ to the infecting nucleocapsid, where it enhances the transcription of the large RNA segment that codes for the capsid proteins. Finally, we relate the structural aspects of bacteriophage Φ6 top those of other dsRNA viruses, noting the similarities and differences.

Chromium poisoning strongly influences the performance of solid oxide fuel cell (SOFC) stacks. A three-dimensional, time-dependent, computational fluid dynamics model of a single channel of a F10 SOFC stack in Forschungszentrum Jülich GmbH is developed to investigate chromium poisoning for different stack designs, temperatures and absolute air humidities. The model takes into account both chemical and electrochemical mechanisms of chromium poisoning and is able to predict the spatial distribution of SrCrO4 and Cr2O3. The voltage degradation over 100 kh can be simulated quantitatively. According to the simulation results, chromium poisoning is almost eliminated by the application of the protective coating fabricated by the atmospheric plasma-spraying (APS) technology. Besides, with the help of the APS protective coating, operating a SOFC stack with less dehumidified air at 650 oC is possible according to the simulation.

To further understand the role of phosphorylation in ISGF3- and STAT2/IRF9-mediated constitutive and long-term IFN-I-stimulated transcriptional responses, we performed RNA-Seq and ChIP-Seq, in combination with phosphorylation inhibition and anti-viral experiments. First, we identified a group of ISRE-containing ISGs that were commonly regulated in IFNα treated WT and STAT1-KO cells. Thus, in 2fTGH and Huh7.5 WT cells IFNα-inducible transcription and anti-viral activity relied on the recruitment of the ISGF3 components STAT1, STAT2 and IRF9 in a phosphorylation- and time-dependent manner. Likewise, in ST2-U3C and Huh-STAT1KO cells lacking STAT1, ISG expression correlated with DNA-binding of phosphorylated STAT2/IRF9. This pointed to a dominant role of classical ISGF3 and STAT2/IRF9, and not U-ISGF3 or U-STAT2/IRF9, in the regulation of early and prolonged ISG expression and viral protection, in WT and STAT1-KO cells. In addition, comparative experiments in U3C (STAT1-KO) cells overexpressing all ISGF3 components (ST1-ST2-IRF9-U3C), revealed a threshold-dependent role of U-ISFG3, and potentially U-STAT2/IRF9, in the regulation of constitutive and possibly long-term IFNα-treated ISG expression and anti-viral activity.

We previously developed a highly sensitive and specific anti-PDPN mAb, LpMab-23 (mouse IgG1, kappa). In this study, we produced a humanized IgG1 version (humLpMab-23) and its defucosylated form (humLpMab-23-f) of an anti‑PDPN mAb to potentiate the ADCC activity. The humLpMab-23 could recognize PDPN‑overexpressed Chinese hamster ovary (CHO)-K1 (CHO/PDPN) and PDPN-positive PC-10 and LN319 cells by flow cytometry. Furthermore, we found that humLpMab-23-f exerted ADCC and complement-dependent cytotoxicity against CHO/PDPN, PC-10 and LN319 cells in vitro and exhibited potent antitumor activities in the xenograft models. These results indicated that humLpMab-23-f could be useful for an antibody treatment regimen for PDPN-positive human cancers.

Many studies on magnetorheological fluid (MRF) have been carried out over last three decades several salient advantages such as fast phase change, easy control of the yield stress and so forth. Especially, several review articles of MRF technology have been reported for last two decades summarizing the development of MRFs and their applications. As specific examples, the review articles including the optimization of the particles and carrier liquid to achieve minimum off-state viscosity and maximum yield stress at on-state, the formulation of many constitutive models in-cluding Casson model and Herschel-Bulkley (H-B) model, the sedimentation enhancement using additives and nanosized particles, many types of dampers for automotive suspension and civil structures, medical and rehabilitation devices, MRF polishing technology, the methods of mag-netic circuit design, and the synthesis of various controllers have been published. More recently, the effect of the temperature and thermal conductivity on the properties of MRFs and application systems are actively being investigated by several works. However, there is no review article on this issue so far despite of that the thermal problem is one of crucial factors to be seriously con-sidered for the development of advanced MRFs and commercial products of application systems. In this work, studies on the thermal conductivity and temperature in MRFs themselves and tem-perature-dependent application systems are reviewed, respectively, and principal results are summarized emphasizing on the followings: how to reduce the temperature effect on the field-dependent properties of MRFs and how to design application system to minimize the thermal effect. It is noted here that the review summary is organized in a chronological format using tables.

Hippocampal neuronal activity generates dendritic and somatic Ca2+ signals, which depending on stimulus intensity, rapidly propagate to the nucleus and induce the expression of transcription factors and genes with crucial roles in cognitive functions. Soluble Amyloid-beta Oligomers (AβOs), the main synaptotoxins engaged in the pathogenesis of Alzheimer's disease, generate aberrant Ca2+ signals in primary hippocampal neurons, increase their oxidative tone and disrupt structural plasticity. Here, we explored the effects of sub-lethal AβOs concentrations on activity-generated nuclear Ca2+ signals and on the Ca2+-dependent expression of neuroprotective genes. To induce neuronal activity, neuron-enriched primary hippocampal cultures were treated with the GABAA receptor blocker gabazine (GBZ), and nuclear Ca2+ signals were measured in AβOs-treated or control neurons transfected with a genetically encoded nuclear Ca2+ sensor. Incubation (6 h) with AβOs significantly reduced the nuclear Ca2+ signals and the enhanced phosphorylation of cyclic AMP response element binding protein (CREB) induced by GBZ. Likewise, incubation (6 h) with AβOs significantly reduced the GBZ-induced increases in the mRNA levels of Neuronal Per Arnt Sim domain protein 4 (Npas4), Brain-derived Neurotrophic Factor (Bdnf), Ryanodine Receptor type-2 (RyR2), and the antioxidant enzyme NADPH-Quinone-Oxidoreductase (Nqo1). Based on these findings we propose that AβOs, by inhibiting the generation of activity induced nuclear Ca2+ signals, disrupt key neuroprotective gene expression pathways required for hippocampal-dependent learning and memory processes.

The cyclin-dependent kinase (Cdk) 1–cyclin B (CycB) complex plays critical roles in cell cycle regulation. Before Drosophila male meiosis, CycB is exported from the nucleus to the cytoplasm via the nuclear porin 62kD (Nup62) subcomplex in the nuclear pore complex. When this is inhibited, Cdk1 is not activated, and meiosis does not initiate. We investigated the mechanism that controls cellular localization and activation of Cdk1. Cdk1–CycB continuously shuttled into and out of the nucleus in the prolonged G2 phase before meiosis. Overexpression of CycB, but not that with nuclear localization signal sequences, rescued reduced cytoplasmic CycB and inhibition of meiosis in Nup62-silenced cells. Full-scale Cdk1 activation occurred in the nucleus shortly after its rapid nuclear entry. Cdk1-dependent centrosome separation did not occur in Nup62-silenced cells, while Cdk1 interacted with Cdk-activating kinase and Twine/Cdc25C in the nucleus of Nup62-silenced cells, suggesting the involvement of another suppression mechanism. Silencing of roughex rescued Cdk1 inhibition and initiated meiosis. Nuclear exports of Cdk1 ensured its escape from inhibition by cyclin-dependent kinase inhibitor. The complex reentered the nucleus via importin β at the onset of meiosis. We propose a model regarding the dynamics and activation mechanism of Cdk1–CycB to initiate male meiosis.

This paper aims to establish a current relationship between pharmaceutical sciences and the development of perfumes and fragrances, which bring significant economic benefits and whose added value is among other professionals, the one made by professionals in Pharmacy. For this purpose, historical data are used as a starting point and galenic, chemical and botanical aspects are discussed in a transversal way. In this sense, it must be taken into account that in the case of Spanish pharmacy, it is closely linked to the knowledge and use of plants. Sources such as Web of Science (WOS) and databases such as Scopus, monographs and various web pages (where scientific-technical documents appear) have been used. The results and discussion are based on the selection of the 50 plant species most commonly used in high quality fragrances. Therefore, this publication should be considered as an approach to this subject based on an analysis of a representative sample of data. Some characteristics of perfumes (classification according to the concentration of essential oils and combination of plant extracts) are presented beforehand. They also briefly compile the traditional and modern ways in the treatment of these extracts. The main focus of this work is the botanical and chemical analysis of these described plants, pointing out their common name, correct botanical name, geographical place of origin, used part of the plant and main molecules. The 50 botanical species belong to 27 families of angiosperms and are represented in a large part of the phylogenetic tree of botanical systematics. The most significant families are aromatic: Rutaceae (16.7%), Lamiaceae (16.7%) and Apiaceae (6.5%). The most represented genus is Citrus (with seven species or hybrids). However, it should be noted that natural extracts of good quality natural fragrances may be supplemented with chemically synthesized molecules. Of the 50 botanical species selected, 84% of the extracts have their origin in Tropical Asia, the Middle East and the Mediterranean region. This figure generally coincides with the percentage of medicinal plants (or their extracts) admitted by the European Pharmacopoeia. All parts of a plant (depending on which one it is) can be a source of molecules for the elaboration of these products. The most commonly used parts to obtain extracts are flowers (34%) and leaves (30%), a biological circumstance that is explained in this work. On the opposite side are the resins (10%), rhizomes and roots (8%). In this work, 110 molecules have been found that are part of the essences of perfumes and fragrances, the most frequent are: linalool, limonene, 1,8-cineole, eugenol and derivatives, geraniol, vanillin and derivatives, β-cariophyllene, p-cmene and farnesene and derivatives (3.64%). However, in order to elaborate a quality perfume, many other molecules must be taken into account, according to the creative experience of the perfumer, which is subject to confidentiality and chemical analysis according to current legislation, which would avoid fraud, allergy and dermatitis problems.

In the present work, we report on a 3D MOF of {[Pb5(3-OH)(3-NO3)3(6-pmdc)3·H2O}n formula (pmdc = pyrimidine-4,6-dicarboxylate) synthesized by an oven-heated solvent-free procedure. The large connectivity afforded by the three ligands in their coordination to lead(II) ions grows cubic building units characterized by a central Pb atom with an unusual coordination index of 12 and six pmdc ligands occupying the faces. These cubic units are linked one another giving rise to a quite condensed structure that represents an unprecedented topology showing the (4.62)6(43)2(45.610)3(45.68.82)6(46.69)6(612.83) point symbol. The crystalline material has been characterized by routine physico-chemical techniques to confirm its purity and its thermal behaviour has been also studied by thermogravimetric and thermodiffractometric analyses. The solid presents greenish blue photoluminescent emission based on pmdc ligands, as revealed time-dependent density-functional theory (TD-DFT) calculations, by that is substantially more intense than in free H2pmdc ligand according to its improved quantum yield. The emissive capacity of the material is further analysed according to decreasing temperature of the polycrystalline sample, finding that sizeable long-lasting phosphorescence is present.

Thermally-assisted-occupation density functional theory (TAO-DFT) has been an efficient electronic structure method for studying the ground-state properties of large electronic systems with multi-reference character over the past few years. To explore the time-dependent (TD) properties of electronic systems (e.g., subject to an intense laser pulse), in this work, we propose a real-time (RT) extension of TAO-DFT, denoted as RT-TAO-DFT. Besides, we employ RT-TAO-DFT to study the high-order harmonic generation (HHG) spectra and related TD properties of molecular hydrogen H2 at the equilibrium and stretched geometries, aligned along the polarization of an intense linearly polarized laser pulse. The TD properties obtained with RT-TAO-DFT are compared with those obtained with the widely used time-dependent Kohn-Sham (TDKS) method. In addition, issues related to the possible spin-symmetry breaking effects in the TD properties are discussed.

Influenza viruses cause acute respiratory infections responsible for significant mortality and morbidity around the world. Various factors, such as antigenic drift, allow influenza strains to avoid being fully suppressed by seasonal vaccines. This has led to the increased scrutiny of antivirals as treatment and prophylaxis options for seasonal outbreaks and potential pandemics. Unfortunately, many influenza antivirals suffer from a lack of adequate clinical trials, as well as a lack of toxicity data. This is especially true of umifenovir (arbidol), a drug popularly used for the prevention and treatment of influenza strains in China and Russia. Neuraminidase inhibitors, though widely prescribed, display a potential for future resistance. Adamantanes, while proven to be effective in treating influenza A, are already encountering rapid and widespread cross-resistance and are effectively obsolete. Baloxavir marboxil, a newer antiviral, shows promise in treating acute uncomplicated influenza and may avoid the development of resistance when co-administered with other antiviral drugs. Indeed, the low genetic barrier to resistance associated with influenza antivirals could potentially be overcome by co-administration with other antivirals. This review explores the most widely prescribed antivirals for influenza treatment, their mechanisms of action, and the data currently available about their susceptibility to resistance and efficacy.

Unidirectional flow of a fluid with pressure-dependent viscosity through a porous structure is considered when the viscosity-pressure relationship is an exponential function of a pressure power function in order to investigate effects of the viscosity-pressure relation on the flow characteristics. The flow is governed by the generalized Brinkman’s equation with constant permeability, and a model flow domain of flow down an inclined porous channel is chosen for the sake of studying flow behaviour. Although the current work considers flow in a constant permeability porous structure, it does represent a first step in studying the more general, flow through a variable permeability porous channel. The arising governing equations are solved numerically using MATLAB and the flow is simulated to illustrate the effects of fluid properties as well as flow and medium parameters on the velocity profiles and shear stress.

The integrated stress response is a signaling network comprised of four branches, each of which senses different cellular stressors, converging on the phosphorylation of eIF2α to depress global translation and initiate recovery. One of these branches is composed of GCN2, which senses cellular amino acid insufficiency and participates in the maintenance of amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is provoked by inhibiting an additional target. In this light, we screened a combination of drugs to identify biologically active compounds which synergize with the GCN2 inhibitor TAP20. First, a panel of 25 compounds was assayed in six cancer cell lines for drug sensitivity. Each compound was then combined with TAP20 at concentrations below their IC50, and the impact on cell growth was assessed. Selected strongly synergistic combinations were further characterised using synergy analyses and matrix-dependent invasion assays. Inhibitors of proteostasis, of the MEK-ERK pathway and pan-CDK inhibitors flavopiridol and seliciclib were found to potently synergize with TAP20 in two of the tested cell lines. Among their common CDK targets is CDK7, which was selectively targeted with THZ-1 and found to synergize with TAP20. Finally, these combinations were found to be partially synergistic when assessed using matrix-dependent invasion assays. However, we found that TAP20 alone was sufficient to restrict invasion at concentrations well below its growth-inhibitory IC50. We conclude that GCN2 can be targeted for treating cancers by polytherapy or even monotherapy.

E-commerce recommendation systems usually deal with massive customer sequential databases, such as historical purchase or click stream sequences. Recommendation systems’ accuracy can be improved if complex sequential patterns of user purchase behavior are learned by integrating sequential patterns of customer clicks and/or purchases into the user-item rating matrix input of collaborative filtering. This reviews focuses on algorithmic techniques of existing E-commerce recommendation systems that are sequential pattern based such as ChoRec05, ChenRec09, HuangRec09, LiuRec09, ChoiRec12, Hybrid Model RecSys16, Product RecSys16, SainiRec17, HPCRec18 and HSPCRec19. It provides a comprehensive and comparative performance analysis of these systems, exposing their methodologies, achievements, limitations, and potentials for solving more important problems in this domain. The review showed that integrating sequential pattern mining of historical purchase and/or click sequences into user-item matrix for collaborative filtering (i) improved recommendation accuracy (ii) reduced user-item rating data sparsity (iii) increased novelty rate of recommendations and (iv) improved scalability of the recommendation system.

The focus of the current research indicates a new Bianchi type-V anisotropic, homogeneous astrophysical model with modified theory of f(R, T) gravity and Λ(t), time-dependent cosmological constant. The significant effect of the model is that the field equations solutions find using a time-dependent quadratic deceleration parameter. We observed anisotropy parameter remains constant both in the belated universe and early universe. The deportment of the equation of state (EOS) parameter, pressure, and energy density, cosmological constant and other parameters are also discussed. This cosmological model indicated the possibility of an accelerating universe with negative pressure, such as a universe dominated by dark energy. Om(z) diagnostic test suggested that the universe starts with quintessence nature and ends as a phantom model. Also, energy conditions of this model are represented here to ensure the model is physically reasonable and based on observations.

Drought stress imposes substantial constraints on the growth and production of wheat (Triticum aestivum L.), a globally important cereal crop that is essential for food security. To mitigate these adverse effects, researchers are intensifying their efforts to comprehend how different genotypes respond to drought stress, aiding in the development of sustainable breeding and management strategies. This review summarized past and recent research on genotype-dependent responses of wheat to drought stress, encompassing morphological, physiological, biochemical, molecular, genetic, and epigenetic reactions in plants. Screening of drought-affected features at early developmental stages can provide valuable insights into the adult growth stages that are closely linked to plant productivity. The review underscores the importance of identifying key traits associated with drought resistance, and the potential of leveraging wheat diversity to select cultivars with desirable agronomic characteristics. It also highlights recent advancements in investigating Bulgarian wheat genotypes with varying levels of drought tolerance, specifically in detecting essential features contributing to drought tolerance. Cultivating drought-resistant wheat genotypes and understanding stress stability determinants could markedly contribute to enhancing wheat production and ensuring stable yields under changing climate conditions.

In this study, we investigated, for the first time, the effects of the spatially varying effective mass, asymmetry parameter, and well width on the electronic and optical properties of the quantum well which has an improved Rosen-Morse potential. Calculations are made within the framework of the effective mass and parabolic band approximations. We have used the diagonalization method by choosing a wave function based on the trigonometric orthonormal functions to find eigenvalues and eigenfunctions of the electron confined within the improved Rosen-Morse potential. Our results show that the position-dependence mass, asymmetry, and confinement parameters cause significant changes in the electronic and optical properties of the structure we focus on since these effects create a significant increase in electron energies and a blue shift in the absorption spectrum. The increase in energy levels enables the development of optoelectronic devices that can operate at wider wavelengths and absorb higher energy photons. This offers potential advancements in fields such as optical communication, imaging technology, and solar cells.

Background: Best Possible Medication History (BPMH) collected by clinical pharmacists is crucial for effective medication review but, in Italy, it is often left to the nursing staff. This study aims to compare the quality and accuracy of a clinical pharmacist-documented BPMH with the current standard practice of ward staff-collected BPMH at an Italian perioperative surgical setting. Methods: A 20-week prospective observational non-profit study was conducted in a major University hospital. The study comprised a feasibility, an observational, and an interventional phase. During the feasibility phase, 10 items for obtaining a correct BPMH were identified. The control group consisted of retrospectively analyzed BPMHs collected by the ward staff during the observational phase, while interventions included BPMHs collected by the clinical pharmacist during the third phase. Omissions between the two groups were compared. Results: 14 (2%) omissions were found in the intervention group, compared with 400 (57.4%) found in the controls (p<0.05); data collection was more complete when collected by pharmacists compared to the current modalities (98.0% versus 42.6%; p<0.05). Conclusions: The involvement of a pharmacist significantly reduced the number of omissions in perioperative surgical-collected BPMHs. This intervention holds the potential to decrease the risk of medication errors associated with inaccurate or incomplete BPMHs prior to surgical hospitalization.

Historical and Endowment Properties are different from Heritage and cultural Properties, as Historical and Endowment properties are governed by a unique set of laws that Waqf recipients must abide by. Property that is entrusted is usually in the form of buildings, land or valuables which in preservation is not limited to time as long as the property can be utilized. Reliable information technology is needed to ensure data security both digitally and physically, while the rapid development of information technology demands information openness and this will be a challenge in itself. The objectives of this study include examining the collection of historical databases and endowments, the relationship between digital data and physical data and management organizations. The method of how to design a query model to display data is then analyzed whether the data conforms to the rules in waqf management. The results are expected to bring up accurate data between digital data and physical data and if there are differences into findings for the next analysis.

In recent years, Machine Learning (ML) has become a buzzword in the petroleum industry with numerous applications which guide engineers in better decision-making. The most powerful tool that most production development decisions rely on is reservoir simulation with applications in numerous modeling procedures, such as individual simulation runs, history matching and production forecast and optimization. However, all these applications lead to considerable computational time and computer resources associated costs, rendering reservoir simulators as not fast and robust enough, thus introducing the need for more time-efficient and smart tools, like ML models which are able to adapt and provide fast and competent results that mimic the simulator’s performance within an acceptable error margin. The first part of the present study (Part I) offers a detailed review of ML techniques in the petroleum industry, specifically in subsurface reservoir simulation, for the cases of individual simulation runs and history matching, whereas the ML-based Production Forecast Optimization applications will be presented in Part II. This review can assist engineers as a complete source for applied ML techniques since, with the generation of large-scale data in everyday activities, ML is becoming a necessity for future and more efficient applications.

A review is here provided about the thermal effects on the optical chirality. To this goal, chiral objects dispersed in an embedding fluid are examined for their magnetoelectric coupling. Thermal effects on several chiral meta-atoms and their ensembles are examined. To this goal, DNA-like helical structures are examined in detail. Mechanical aspect of thermo-elasticity is reviewed along with transverse deformations, while drawing analogies from condensed-matter physics. In this respect, chirality-induced spin selection is reviewed along with the temperature-mediated elec-tron-phonon interactions. A wide range of materials such as polymers and biological cells are also examined for temperature effects. A transition temperature delineating a sign flip in the chirality parameter is identified as well. Chirality-associated functionalities such as ratchet motions, switching, and modulations are investigated for their respective thermal effects. Issues of fabri-cating chiral meta-atoms are also discussed.

Despite being a rare disease worldwide, rabies has the highest morbidity and mortality rates, with nearly all symptomatic cases leading to coma and death. Rabies represents an infectious disease caused by the Rabies virus (RABV), which is part of the Lyssavirus group and the Rhabdoviridae family, and it mainly spreads through the bite and scratch of an infected mammal, but particularly of wild animals, such as bats, foxes, wolves and racoons, and of domestic animals, such as dogs and cats, in rabies-prone areas of the world. Airborne transmission has been deemed as extremely rare, and no clinical case as such has been recorded worldwide yet, except in the enclosed environment, such as research laboratories and caves where infected bats are present. Domestic mammals, such as dogs and ferrets, represent other important reservoirs of disease transmission, and the human cases of Asia and Africa amount approximately 95% of all human cases worldwide. Infected animals most commonly start transmitting the virus once the first symptoms have occurred, and if they experience disease aggravation and death within 10 days, a case of rabies is registered, more easily if the incidence occurred in the urban area and then, any person or animal that had been potentially exposed are strongly recommended to receive the inoculation. It is rare for asymptomatic mammals to transmit the illness. Most First-World and several Second-World countries have recently been declared dog rabies-free by the World Health Organization. The disease can only be treated prophylactically, with three doses of a vaccine containing an inactivated form of RABV, or with five doses of the vaccine and two doses of anti-RABV immunoglobulins within 28 days if the patient is believed to have been exposed to the virus beforehand. It has been projected that, once the viral load reaches elements of the central nervous system, prophylactic approaches are no longer effective, even if symptoms have not begun yet, and this highlights the urgent trait of the medical condition, strongly recommending exposed people to receive the prophylactic doses immediately after the potential exposure to the virus. The pathogen first infects the bodily fluids, before reaching the peripheral nervous system, from where it will gradually move toward the spinal cord or the encephalon, at a speed of movement ranging from 1 to 40 cm per day. It was also found, in extremely rare circumstances, to infect the nasopharyngeal cavity and the lungs. The primary cause of a successful, gradual advance of the viral load toward the point of clinical no-return for the patient - the CNS - is a complex mechanism of induced innate immune evasion, with the interferon system being heavily targeted and silenced by RABV proteins. The ‘Milwaukee’ protocol is locally believed to decrease the mortality rate of the clinical illness to approximately 80%, although significantly more research is required in this sense. First-line immune evasion represents the central mechanism developed by viruses during their evolutionary process to gain control over human immunity, so it could be the development and adjustment of a counter-offensive to this evolutionary operating system that could address the core elements of the problem. Human recombinant Type I and Type III Interferons were found to be significant vaccine adjuvants and to considerably delay the clinical onset of the disease. Despite their central role in natural immunity-based prophylaxis, vaccine support and, in often cases, vaccination per se, a local administration of IFNs as such may not be enough to tackle the core problem of the endemic disease, and a specific and systemic treatment of potential host cells with IFN I and III, as well as IFN-stimulating proteins, may constitute a major research requirement in the coming years of disease investigation, as the inoculation efforts with the inactivated virus and immunoglobulin administration continue. The administration of a relatively low dosage of somatic Natural Killer cells, gamma-interferon and perhaps, of somatic helper CD4+ and somatic cytotoxic CD8+ T-lymphocytes treated with alpha-, beta- and lambda-interferon could be merged with the administration of a similar dosage of alpha-, beta- and lambda-interferon during the efforts to develop an effective and less costly prophylactic vaccine against rabies. A combination of a nasal substance containing a low dosage of IFN I and III with a reduced concentration of neutralized RABV copies, and/or with a low dose of anti-RABV IgA antibodies, could also be tested for humans for the purposes of pre- and post-exposure prophylaxis.

Vitamin E is a group of eight compounds divided into two subgroups: four tocopherols (α-, β-, γ-, and δ-) and four tocotrienols (α-, β-, γ-, and δ-). α-Tocopherol is considered the most biologically active form. This review paper summarizes the current knowledge and historical progression of vitamin E research, with particular emphasis on its role in animal nutrition. Early studies in the 1920s identified vitamin E’s role in preventing neonatal mortality in rats. Over the following decades, scientists discovered the compound’s chemical structure and its importance for the immune system, skin health, anti-inflammatory properties, hormonal balance, and other bodily functions. Production of vitamin E products has evolved, starting with isolating the vitamin from natural sources and advancing to synthesizing it with greater efficiency and standardized potency units. Early animal studies focused on reproductive health and growth disorders, but further research demonstrated the importance of vitamin E in preventing encephalomalacia in domestic fowl and muscular dystrophy in rabbits and other animals. Today, vitamin E is commonly used as a feed additive to meet animals’ requirements and assure immune function and overall health. Despite much knowledge on vitamin E’s role in animal nutrition, many questions remain unanswered, and current research aims to determine optimal supplementation levels, interactions with other nutrients, impacts on gene expression, cell signaling and communication, and effects of supranutritional dosages in livestock. Vitamin E has a long and fascinating history in scientific research, with significant advancements in understanding its chemical structure and biological activity. In animal nutrition, vitamin E continues to play an important role in improving animal health, and ongoing research will continue to expand our understanding of its benefits and mechanisms of action.

Two monoclonal antibodies (mAbs) against human epidermal growth factor receptor 2 (HER2), trastuzumab and pertuzumab, were clinically approved. We previously developed a highly sensitive and specific anti-HER2 mAb, H2Mab-139 (mouse IgG1, kappa). In this study, we produced a defucosylated IgG2a version of anti‑HER2 mAb (H2Mab-139-mG2a-f) to enhance ADCC-mediated antitumor activity. H2Mab-139-mG2a-f exhibits a high binding affinity in flow cytometry with the dissociation constant (KD) determined to be 3.9 × 10‑9 M and 7.7 × 10‑9 M against HER2‑overexpressed Chinese hamster ovary (CHO)-K1 (CHO/HER2) and HER2-positive BT-474 cells, respectively. Moreover, we showed that H2Mab-139-mG2a-f exerted ADCC and complement-dependent cytotoxicity against CHO/HER2 and BT-474 cells in vitro and exhibited potent antitumor activities in the xenograft models. These results indicated that H2Mab-139-mG2a-f exerts antitumor effects against HER2-positive human breast cancers and could be useful for an antibody treatment regimen for HER2-positive human cancers.

Creep is a fundamental property naturally exists in some types of rock, which is significant for the long-term stability of roadways during the mining process. In this paper, the long-term strength of coal and rock were obtained via laboratory experiments, and a Cvisc elasto-viscoplastic model was adopted and introduced in FLAC3D, based on the 3101 transport roadway in Hongqinghe Coal Mine, to investigate the influence of creep on the stability of deep-high stress roadway. The test results show that the long-term strength of 3-1 coal and sandy mudstone, respectively, is 18.65 MPa, 39.95 MPa. The plastic zone, the deformation, and the damage of roadway surrounding rock behave an obvious increase after being excavated for 720d as the creep model was chosen. The plastic zone failure with models shear-p (1090.7 m3), shear-n (381.7 m3), tension-n (98.4 m3), and tension-p (30.8 m3), the damage value has an obvious increment of increased 21.2% (0.053), the deformation increases in the order is two-sidewalls (1978 mm), roof (907 mm), floor (101 mm). The creep of the roadway can be divided into three stages: the accelerating stage, the decaying stage, and the stable stage. The creep speed of each stage is greatly affected by the presence or absence of anchor spray support: the creep speed of the bare roadway roof, roadway side, and floor stability, respectively, is 1.01, 1.02, and 0.12 mm/d; After anchor spray support, the creep velocity, correspondingly, decreased to 0.69, 0.37, and 0.12 mm/d, and the amount of surrounding rock damage decreased from 0.302 to 0.243. This indicates that the anchor spray support can significantly reduce the creep effect of the roadway. The Cvisc creep model was verified reliable and can provide guidance for deep high-stress coal roadway support.

Durability of concrete requires a dense microstructure which can be achieved by using self-compacting concrete (SCC). Both calcined clay (CC) and rice husk ash (RHA) are promising supplementary cementitious materials (SCMs) that can partially replace cement, but their use in SCC is critical due to their higher water demand and specific surface area (SSA) compared to cement. Empirical method of SCC design was adopted considering the physical properties of both CC and RHA. The influence of partially substituting cement at 20 vol-% with binary and ternary blends of CC and RHA were investigated. The fresh properties of SCC were investigated using a variety of tests. The time dependent workability was monitored by plunger method and flow resistance determined based on the rheological measurements of SCC. The evolution of the hydrate phases of the binder in SCC was determined by thermogravimetric analysis, while the durability was evaluated by rapid chloride migration test. Cement partial replacement with 20 vol-% CC has no significant effect on SCC fresh, time dependent, compressive strength and durability properties. 20 vol-% RHA on the other hand requires higher dosage of SP to achieve self-compactability and increased the viscosity of SCC. Its workability retention is only up to 30 min after mixing and exhibited higher flow resistance. It consumes more CH and improves compressive strength and chloride resistance of SCC. The ternary blending with CC and RHA yielded better fresh SCC properties compared to the binary blend with RHA, while an improved chloride penetration resistance could be achieved compared to binary CC blend.

Typhulaceae Jülich is one of the cold-adapted fungal families in basidiomycetes. Typhula (Pers.) Fr. and Pistillaria Fr. representing the family are distinguished from the morphology of a stipe to a hymenium (Fries 1821). The hymenium of Typhula is distinguishable from the stipe, but indistinguishable and consecutive in the genus Pistillaria. This taxonomic criterion is ambiguous, and consequently the opinion of Karsten (1882) has been widely accepted; I the genus Typhula, basidiomata develop from sclerotia, while basidiomata develop directly from substrata in the genus Pistillaris. But, Corner (1970) observed basidiomata of Pistillaria petasitis S. Imai in Hokkaido, Japan, from sclerotia. We collected irregular sclerotia of Typhula hyperborea H. Ekstr. from Upernavik, West Greenland. This specimen had a stipe-like structure on a Poaceae plant, and sclerotia developed on its tip. In August, P. petasitis in Hokkaido, Japan, formed basidiomata directly from substrates on the ground. Similar phenomena were found from other Typhula spp. in Japan. All of these fungi had the potential to produce sclerotia in culture, and as well as the capacity of mycelial growth at ambient air temperatures in each locality when samples were collected. These findings suggest that Typhula spp. developed basidiomata not only from the sclerotia dispersed by the basidiospores but also mycelia generated by the spore germination formed basidiomata multiple times depending on their growth environments.

Fish tissue samples from 203 adult individuals were collected in the main ports and markets of the Pacific coast of Panama. Molecular identification based on cytochrome oxidase I gene segment of all species was verified GENBANK reference sequences. 34 species from 14 families (Ariidae, Lutjanidae, Caranjidae, Scianidae, Centropomidae, Serranidae, Scombridae, Sphyraenidae, Haemulidae, Gerreidae, Stromotidae, Lobotidae, Malacanthidae, Mugilidae) were identified at species molecular level from 164 sequences. Also, three Caribbean species were molecularly identified among the analyzed samples (Mycteroperca xenarcha, Paralonchurus brasilensis and Lobotes surinamensis). Species diversity was slightly higher in the Gulf of Panama than in the Gulf of Chiriquí. For species with 5 or more individual sequences, genetic diversity and genetic connectivity parameters such as: total number of haplotypes (H), haplotype diversity (Hd), and nucleotide diversity (π) were calculated. Overall, pelagic-migratory species showed higher values of genetic diversity than coastal and estuarine species with some exceptions. Connectivity between Gulf areas was compared using values of genetic distances and genetic differentiation (Fst). High level of connectivity observed between Gulf of Chiriqui and Gulf of Montijo indicates the existence of a single stock in that area for the following species: Scomberomorus sierra, Caranx caninus and Lutjanus guttatus. Demographic history of the most common species was examined using Tajima’s D values suggesting population expansion for two snapper species, L. peru and L. argentiventris, having significant and higher values. Another important contribution from this research was the production of primers and dual labeled probes for environmental DNA detection using qPCR for the five most abundant species (spotted rose snapper, yellow snapper, green jack, Pacific crevalle jack and the Pacific sierra fish). These markers represent a new set of tools for environmental DNA (eDNA) detection and molecular traceability of three commercially important fish species along the supply chain including landing sites and markets of the main fishery areas.

Thalassemia is a heterogeneous congenital hemoglobinopathy common in the Mediterranean region, Middle East, Indian subcontinent, and Southeast Asia with increasing incidence in Northern Europe and North America due to immigration. Iron overloading is one of the major long-term complications in patients with thalassemia and can lead to organ damage and carcin-ogenesis. Hepatocellular carcinoma (HCC) is one of the most common malignancies in both transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). The incidence of HCC in patients with thalassemia has increased over time, as better chelation therapy confers a sufficiently long lifespan for the development of HCC. The mechanisms of iron overloading-associated HCC development include the increased　reactive oxygen species (ROS), inflammation cytokines, dysregulated hepcidin, and ferroportin metabolism. The treat-ment of HCC in patients with thalassemia was basically similar to those in general population. However, due to the younger age of HCC onset in thalassemia, regular surveillance for HCC development is mandatory in TDT and NTDT. Other supplemental therapy and experience of novel treatment for HCC in thalassemia population were also reviewed in this article.

Due to the influence of bio-geographical and environmental factors, as well as anthropogenic landscape features, organism shows different reproductive strategies among different populations. There is lack of detailed information on the reproductive biology of Kentish plover Charadrius al-exandrinus in arid lands in Central Asia. In this study, we summarized the characteristics of the reproductive biology of three geographically distinct plover populations in Aibi Lake in the Northwestern Xinjiang, Taitema Lake in the Southern Xinjiang and artificial reservoirs around Urumqi City in Northern Xinjiang respectively, based on 440 eggs of 158 nests observed and ana-lyzed from April to July of 2019 and 2020. We find that there is no significant difference in clutch size among the three populations. However, the egg size of Taitema Lake population is signifi-cantly larger than those of the other two populations, whilst egg volume and clutch volume of ar-tificial reservoirs population are significantly larger than that of Aibi Lake. With the postpone-ment of laying date, the northern and northwestern populations respectively show the character-istics of small clutch size and relatively small egg size, and decrease of reproductive outputs. The heavier female plovers in Taitema Lake lays eggs earlier, and there was significantly positive cor-relation between the female body mass and the clutch size and egg size. The tarsometatarsus length of the female plovers was significantly positively correlated with the reproductive output in all three populations. The model selection results show that female body size and ambient tem-perature restrict the egg size and reproductive output of Kentish plovers, which is consistent with the upper limit hypothesis of the maternal condition and the maternal constraint. Our data sup-port that Kentish plover show distinct flexibility in breeding strategies to cope with the harsh nat-ural environment in arid lands of Xinjiang, China. The results of relatively high average clutch size and average egg size imply that saline wetlands in Western China are important breeding habitats for Kentish plover.

The major goal of this work is to present a novel fractional temperature-dependent boundary element model (BEM) for solving thermoelastic wave propagation problems in smart nanomaterials. The computing performance of the suggested methodology was demonstrated by using stable communication avoiding S-step – generalized minimal residual method (SCAS-GMRES) to solve discretized linear BEM systems. The benefits of SCAS-GMRES are investigated and compared to those of other iterative techniques. The numerical results are graphed to demonstrate the influence of fractional, piezoelectric, and length scale characteristics on total force-stresses. These findings also demonstrate that the BEM methodology is practical, feasible, effective, and has superiority over domain methods. The results of the present paper help to develop the industrial uses of smart nanomaterials.

The way humans use natural resources and especially freshwater, reflects their relationship with nature. It also influences the conceptual Water Resources Management (WRM) model. A historical review shows that the interplay between Humans and Nature is diachronically in constant change between two opposites: conflict and cooperation. Lessons from the past 20.000 years indicate that the WRM model is a function of two main parameters: (1) socio-economics, and (2) climate conditions. Three different Eras of the Humans-Nature relationship have been distinguished: (1) Naturalistic: Nature dominating Humans during the Last Glacial Period (100-10) kyr BC, (2) Dualistic: Nature-Humans cooperation and competition from 10 kyr BC to 1800 AD, and (3) Anthropocentric: Humans dominating Nature from 1800 AD to now. Since 2000, the Integrated WRM (IWRM) model is promoted as state-of-the-art and remains anthropocentric producing huge externalities. Its assessment during the last 20 years has given mixed results and needs to be reformulated. The new model we suggest is based on the dialectical tool for conflict resolution. It unifies Humans and Nature and enhances the social dimension of WRM. After identifying conflicts between stakeholders and the natural laws (eristic part), opposite objectives are unified to harmonize Humans with Nature (dialectical resolution). A case study of flood mitigation illustrates the eristic-dialectical methodology.

The dynamic response of a Bell-and-Bloom magnetometer to a parallel (to the bias field) time-dependent field is modelled beyond the commonly assumed quasi-static regime. The results unveil features that are related to the parametric nature of the considered system. It is shown that a for low-amplitude time-dependent field different operating conditions are possible and that, beside the commonly reported low-pass-filter behaviour, a band-pass response emerges. Moreover, we numerically show that for larger field amplitude the system, due to its parametric nature, has a kind of ``non-linear'' response.

Barry Turner’s 1978 Man-made Disasters and Charles Perrow’s 1984 Normal Accidents were seminal books but a detailed comparison has yet to be undertaken. Doing so is important to establish content and priority of key ideas underpinning contemporary safety science. Turner’s research found socio-technical and systemic patterns that meant that major organisational disasters could be foreseen and were preventable. Perrow’s macro-structuralist industry focus was on technologically deterministic but unpredictable and unpreventable ‘system’ accidents, particularly rare catastrophes. Andrew Hopkins and Nick Pidgeon respectively suggested that some prominent writers who wrote after Turner may not have been aware of, or didn’t properly acknowledge, Turner’s work. Normal Accidents didn’t cite Turner in 1984 or 1999. Using a methodology involving systematic reading and historical, biographical and thematic theory analysis, a detailed review of Turner’s and Perrow’s backgrounds and publications sheds new light on Turner’s priority and accomplishment, highlighting substantial similarities as well as clear differences. In a previously unpublished letter, Perrow confirmed reading Man-made Disasters while writing Normal Accidents. Turner became better known after a 1997 second edition but under-acknowledgment issues continued. Ethical citation and potential reasons for under-acknowledgment are discussed. It is concluded that Turner’s foundational importance for safety science should be better recognised.

RNA interference is a highly conserved process in which non-coding small RNAs (sRNA) modulate gene expression at the post-transcriptional level influencing plant growth and development. Dicer-like (DCL), Argonaute (AGO) and RNA-dependent RNA polymerase (RDR) are the core elements involved in gene silencing and their gene families have been explored in many plants. However, these genes and their response to abiotic stresses have not yet been well in wheat. In this study, 82 AGO, 31 DCL, and 31 RDR genes were identified and phylogenetic analysis of these proteins showed that clustered into ten, four and four clades respectively. RNA-seq analysis revealed constitutive expression of AGO1, AGO9, and DCL2 family expression analysis in tissues under normal and stress conditions, whereas RDR1 which is known to engage in siRNA biogenesis showed higher expression levels in wheat leaf tissues. Our findings build the foundation for comparative genomics analyses of RNA silencing elements in cereal crops, as well as new insights into the functional complexity of RNA silencing in wheat stress responses, which is critical for understanding the processes underlying wheat stress responses.

In this article, we delve into the intricate behavior of electronic mechanisms underlying NMR magnetic shieldings, σ, in molecules containing heavy atoms such as cadmium, platinum, and mercury. Specifically, we explore PtXn^{−2} (X = F, Cl, Br, I; n = 4, 6) and XCl2 Te2 Y2 H6 (X = Cd, Hg; Y = N, P) molecular systems. It is known that the leading electronic mechanisms responsible for the relativistic effects on σ are well characterized by the linear response with elimination of small components model (LRESC). In this study, we present results obtained from the innovative LRESC-Loc model, which offers the same outcomes as the LRESC model but employs localized molecular orbitals (LMOs) instead of canonical MOs. These LMOs provide a chemist’s representation of atomic core, lone pairs, and bonds. The whole set of electronic mechanisms responsible of the relativistic effects can be expressed in terms of both non-ligand-dependent and ligand-dependent contributions. We elucidate the electronic origins of trends and behaviors exhibited by these di- verse mechanisms in the aforementioned molecular systems. In PtX4^{−2} molecules, the predominant relativistic mechanism is the well-established one-body spin-orbit (σ^SO(1) ) mechanism, while the paramagnetic mass-velocity (σ^Mv ) and Darwin (σ^Dw ) contributing mechanisms also demand con- sideration. However, in PtX6−2 molecules, the σ Mv+ Dw contribution surpasses that of the SO(1) mechanism, thus influencing the overall ligand-dependent contributions. As for complexes con- taining Cd and Hg, the ligand-dependent contributions exhibit similar magnitudes when nitrogen is substituted with phosphorus. The only discrepancy arises from the σ^SO(1) contribution, which changes sign between the two molecules due to the contribution of bond orbitals between the metal and tellurium atoms.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) lymphocytes eliminates cells infected with viruses. Antiviral ADCC requires three components: 1) antibody; 2) effector lymphocytes with the Fc-IgG receptor CD16A; and 3) viral proteins in infected cell membranes. Fc-afucosylated antibodies bind with greater affinity to CD16A than fucosylated antibodies; individuals’ variation in afucosylation contributes to differences in ADCC. Current assays for afucosylated antibodies involve expensive methods. We report an improved bioassay for antibodies that support ADCC which encompasses afucosylation. This assay utilizes externalization of CD107a by NK-92-CD16A cells after antibody recognition. We used anti-CD20 monoclonal antibodies, GA101 WT or glycoengineered (GE), 10% or ~50% afucosylated, and CD20-positive Raji target cells. CD107a increased detection 7-fold compared to flow cytometry to detect Raji-bound antibodies. WT and GE antibody effective concentrations (EC50s) for CD107a externalization differed by 20-fold, with afucosylated GA101-GE more detectable. The EC50s for CD107a-externalization vs. 51Cr cell death were similar for NK-92 CD16A and blood NK cells. Notably, the %CD107a-positive cells negatively correlated with dead Raji cells and was nearly undetectable at high NK:Raji ratios required for cytotoxicity. This bioassay is very sensitive and adaptable to assess anti-viral antibodies but unsuitable as a surrogate assay to monitor cell death after ADCC.